The role of high-dose methotrexate in T-cell acute lymphoblastic leukemia treatment: multicenter study results of ALL IC-BFM 2002 protocol

Backround. A progress in Tcell acute lymphoblastic leukemia (TALL) treatment has been achieved in recent years by use a combination of riskadopted chemoradiation therapy, based on highdose (5000 mg/m²) methotrexate. A prerequisite for successful therapy is carefully follow supportive care principles and recommendations, which include blood serum methotrexate concentration monitoring, leucovorin rescue and alkaline solutions use for the best methotrexate elimination and decrease its toxic effects.

Aim. To assess the effectiveness of ALL ICFM 2002 protocol based on highdose methotrexate for Tcell acute lymphoblastic leukemia.

Materials and methods. From 2003 to 2023 in retroprospective study 67 patients with primary diagnosed TALL were enrolled. Median age was 7.4 years (from 0 to 18 years). All the patients were treated according to riskadopted ALL ICFM 2002 protocol. The therapy efficacy was assessed by overall (OS), eventfree (EFS) and relapsefree survival analysis. The survival rates were calculated with statistic program SSS 21.0 by Kaplan–Meier method.

Results. The use of highdose methotrexate for TALL treatment in ALL ICFM 2002 protocol secure high survival rates: 10‑year OS was 82.5 ± 3 %, EFS – 79.3 ± 3 %. Analyzing OS and EFS depending on prognostic risk group we found that standard risk patients had OS and EFS 85.4 ± 6.9 and 78.4 ± 8 %, intermediate – 85.6 ± 6.7 and 82 ± 7.3 % and highrisk – 34.6 ± 18.3 and 20.8 ± 17.1 % respectively (р >0.05).

Conclusion. ALL ICFM 2002 protocol for TALL includes highdose (5000 mg/m²) methotrexate is an effective for standard and intermediate risk patients, but for TALL patients with unfavorable prognostic factors it is necessary a therapy modification by additional cytotoxic and targeted options (nelarabine and daratumumab) inclusion and widening the indications for allogeneic stem cell transplantation.

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